Ahmed J. Alzahrani, Samar El-Shahidy, Najla El Bizri, Ahmed Elsadek Fakhr, Azza El Sheikh, Abid Mahmoud, Md Shadab Shamsi, Fizza Khalid, Hassan Meashi, Huyam Abdelgabar Mohammed, Hamed ALMALKI, Hameed Alhadi, Shyni George, Saleh Al-Odhaybi, Ahmed M. Alfaran, Khalid M. Sumaily, Ahmad Ali Alharbi, Omar Alswailmi, Mohammed Almohammadi, Ibrahim Al-Marshad, Mohammed Alsaadan, Ahmed Al-Akedi, Omar Al Mugren, Osamah Khojah
BACKGROUND: Post-COVID-19 respiratory pathogen dynamics remain incompletely characterized, particularly in the Arabian Peninsula. Understanding pathogen prevalence, co-infection patterns, and age- and season-specific trends is critical for informing diagnostic strategies, public health monitoring, and prevention strategies. METHODS: We conducted a retrospective, multicenter study across seven tertiary hospitals in three Saudi Arabian regions (Riyadh, Jeddah, Qassim), analyzing 23,074 respiratory samples collected from June 2024 to August 2025 using the QIAstat-Dx Respiratory SARS-CoV-2 Panel (QIAGEN, Hilden, Germany). Demographic, seasonal, and co-infection patterns were assessed and determinants of infection were evaluated. Age-specific and pathogen-specific odds ratios with 95% confidence intervals were calculated using multivariable logistic regression, adjusting for sex, region, and season, with adults aged 18-49 years as the reference group. RESULTS: At least one respiratory pathogen was detected in 10,505 samples (45.5%). Single-pathogen infections predominated (88.1%), while co-infections were relatively uncommon (11.9%). Viral pathogens accounted for the majority of detections, with significant age- and region-specific differences identified in multivariable analysis. The most frequently detected pathogens included rhinovirus/enterovirus, influenza A, and RSV, whereas bacterial pathogens were infrequent. Children demonstrated significantly higher odds of adenovirus (adjusted OR 2.8, 95% CI 2.4-3.3), bocavirus (adjusted OR 6.1, 95% CI 4.9-7.6), and RSV (adjusted OR 4.2, 95% CI 3.8-4.7) compared to adults aged 18-49 years, while RSV detection was also elevated in older adults (≥65 years: adjusted OR 2.1, 95% CI 1.8-2.5). Detection rates varied significantly by season, with higher activity in winter and autumn and reduced activity during summer. CONCLUSIONS: Contemporary respiratory infections in Saudi Arabia are dominated by viral pathogens, with age-specific and seasonal patterns resembling pre-pandemic epidemiology. These findings support targeted monitoring, age-stratified prevention strategies, and evidence-based resource allocation for respiratory disease management in the post-pandemic era.